Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

Kadam, Santosh T.; Thirupathi, Ponnaboina; Kim, Sung Soo

doi:10.1016/j.tet.2010.01.010

Cited by 19 publications

(15 citation statements)

References 54 publications

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“…Interestingly, N , O -acetal 4a underwent efficient reactions with different electron-rich (hetero)arenes in the presence of 5 mol % Bi(OTf) 3 , , leading to the formation of the three amidoalkylation products 13a–c in 61–92% yield (Scheme ). In all cases, the shown anti-diastereomer was formed as a major isomer with a high degree of diastereoselectivity.…”

Section: Resultsmentioning

confidence: 73%

“…1 H NMR (400 MHz, CDCl 3 ) δ 7. 2H),3H),7.55 (d,J = 7.3 Hz,1H), 7.49 (t, J = 7.5 Hz, 2H), 7.33 (d,J = 8.2 Hz,2H),1H), 3.62 (qd, J = 7.2, 4.0 Hz, 1H), 3.24 (s, 3H), 2.44 (s, 3H), 1.43 (d,J = 7.3 Hz,3H). (Peaks only for the major diastereomer.)…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…R f (n-hexane/EtOAc = 7:3) 0.28. 1 H NMR (400 MHz, CDCl 3 ) δ 7.77 (d,J = 7.4 Hz,4H),7.61 (d,J = 7.3 Hz,2H), 7.41 (s, 2H), 7.33 (t, J = 6.8 Hz, 5H), 6.27 (d, J = 10.5 Hz, 1H), 6.00 (d,J = 10.0 Hz,1H),5.15 (ddd,J = 24.0,10.2,3.3 Hz,1H),2H), 4.24 (dt, J = 10.1, 5.1 Hz, 1H), 3.50 −3.40 (m, 1H), 3.39−3.33 (m, 1H), 3.24 (s, 1H), 3.17 (s, 2H), 2.43 (s, 4H), 1.36 (dd, J = 6.9, 4.2 Hz, 3H). 13 C{ 1 H} NMR ( 101MHz, CDCl 3 ) δ 156.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Iron(III)-Mediated Oxysulfonylation of Enamides with Sodium and Lithium Sulfinates

et al. 2020

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An iron-mediated vicinal difunctionalization of enamides and enecarbamates with sulfinic acid salts and alcohols is described. This reaction proceeds under mild conditions and furnishes the oxysulfonylated products in moderate to excellent yields. Moreover, the direct incorporation of sulfur dioxide into the sulfonylated products via organolithium chemistry has been achieved. The formed NO -acetals are competent acylimine precursors. Their utilization as building block for the synthesis of biologically relevant β-amidosulfones is described as well. Introduction: Molecules bearing sulfonyl-derived functional groups, such as sulfones or sulfonamides, play an important role in organic chemistry and are widely used in various fields. 1,2 Among the different classes of sulfonyl-derived functional groups, sulfones are of particular interest. They display intriguing chemical and physical properties as well as interesting biological activities. Sulfones, which are often considered as chemical chameleons 3 , are versatile building blocks in organic synthesis. The sulfone motif can be found in various molecules with different applications ranging from agrochemcials and functional materials to active pharmaceutical ingredients. 2-4 Traditional approaches for the construction of sulfones include Friedel-Crafts type reactions of arenes with sulfonyl chlorides 5 , the oxidation of sulfides and sulfoxides 6 , addition reactions of sulfonyl radicals to alkenes and alkynes 7 or the electrophilic trapping of sulfinic acid salts 8,9. In the last ten years novel approaches based on the direct incorporation of sulfur dioxide 10, 11 or the functionalization of C-H bonds 12,13 have emerged as attractive and more sustainable alternatives.

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Section: Resultsmentioning

confidence: 73%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Iron(III)-Mediated Oxysulfonylation of Enamides with Sodium and Lithium Sulfinates

et al. 2020

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“…The latter, however, has only been superficially explored, again mainly using carbamates, although some individual examples with benzamides are present. 13 , 14 , 18 − 21 Also, in the corresponding paper by Petrini, only aromatic aldehydes were found to be reliable reaction partners. 13 Yields decreased with aliphatic aldehydes and these substrates were not further explored.…”

Section: Introductionmentioning

confidence: 92%

Strecker-Derived Methodology for Library Synthesis of N-Acylated α-Aminonitriles

et al. 2021

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The Strecker reaction is a three-component condensation of an aldehyde, an amine, and hydrogen cyanide, delivering an α-amino carbonitrile. Despite extensive investigations, the possibility to use amides instead of amines as one of the three condensation partners has been largely neglected. Nonetheless, the N-acylated α-aminocarbonitriles that are obtained in this way are of direct interest for drug discovery, because they make up a well-known class of mechanism-based inhibitors of serine-and cysteinetype hydrolases. In response, we have thoroughly explored the corresponding variant of the Strecker reaction, focusing on catalyst use, solvent, reaction time, and cyanide source. Optimized parameters were combined in a sequential one-pot protocol for which the scope was found to be compatible with library synthesis applications. Product yields ranged from 7 to 90%, and conditions were found to be mild and tolerant to a wide range of functional groups, including moieties that are typically present in druglike molecules.

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“…257 Kim and co-workers have reported an efficient BiBr 3 -catalyzed synthesis of a-amino nitriles via the nucleophilic addition of trimethylsilyl cyanide to N-acyliminium ions that are generated from a-amido p-tolylsulfones (Scheme 162). 258 Zhan and Li have reported a BiCl 3 -catalyzed three-component synthesis of a-aminophosphonates involving an aldehyde or a ketone, an amine and a dialkylphosphite (Scheme 163). 259 A similar synthesis of a-aminophosphonates catalyzed by Bi(NO 3 ) 3 Á5H 2 O (10.0 mol%) has been reported by Bhattacharya and Kaur (Scheme 164).…”

Section: C-n Bond Formationsmentioning

confidence: 99%

Applications of bismuth(iii) compounds in organic synthesis

2011

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8388 5.3. Formation of acetals catalyzed by bismuth(III) triflate 8388 5.4. Formation of 1,l-diacetates (acylals) 8389 5.5. Cleavage of epoxides catalyzed by bismuth(III) chloride 8389 5.6. Glycosylation promoted by bismuth(III) chloride 8389 5.7. Selective hydrolysis of aryl esters using bismuth(III) mandelate 5.8. Carbon-sulfur bond formation 5.8.1. Synthesis of thioacetals 8389 5.8.2. Conversion of epoxides to thiiranes 8390 5.9. Sulfonylation of aromatics 8390 5.10. Synthesis of sulfides and selenides promoted by Sm-BiCI3 8391 5.11. Synthesis of allyl sulfides 8391 5. 12. Formation of carbon-halogen bonds 8391 5.12.1. Synthesis of �-haloketones and esters 8391 5.12.2. Chlorination of alcohols catalyzed by bismuth(III) salts 8391 5.12.3. Synthesis of peracetylated glycosyl halides 8392 6. Reductions with bismuth compounds 8392 6.1. Selective reduction of nitro compounds to azoxy compounds 8392 6.2. Reduction of nitro compounds to amines 8392 6.3. Chemoselective reduction of a,�-unsaturated ethyl esters using BiCI3-NaBH 4 8392 6.4. Reduction of aromatic a-haloketones 8393 6.5. Miscellaneous reductions 8393 7. Rearrangements promoted by bismuth(III) salts 8393 7.1. Rearrangement of epoxides 8393 7.2. Allylic rearrangement of glycols (the Ferrier rearrangement) 8394 8. Conclusions

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Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

Cited by 19 publications

References 54 publications

Iron(III)-Mediated Oxysulfonylation of Enamides with Sodium and Lithium Sulfinates

Iron(III)-Mediated Oxysulfonylation of Enamides with Sodium and Lithium Sulfinates

Strecker-Derived Methodology for Library Synthesis of N-Acylated α-Aminonitriles

Applications of bismuth(iii) compounds in organic synthesis

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